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Lancet Diabetes Endocrinol. 2014 Nov;2(11):885-93. doi: 10.1016/S2213-8587(14)70174-3. Epub 2014 Sep 1.

Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes.

Collaborators (287)

Donnelly T, Gerstman M, Linjawi S, Park K, Roberts A, Shaw JE, Wu T, Aggarwal N, Bowering K, Chouinard G, DeYoung P, Dumas R, Elliott TG, Frechette A, Giguere N, Gottesman I, Ho K, Kohli S, Teitelbaum I, Tytus R, Wharton S, Woo V, Hellsten T, Kuusela M, Sarti C, Strand J, Valli K, Erlinger R, Goelz S, Hauser KH, Hilgenberg J, Kaiser M, Marck C, Merfort F, Milek K, Paschen B, Rose L, Schlecht K, Wenzl-Bauer V, Dudas M, Fulop G, Harcsa E, Kerenyi Z, Szőcs A, Takacs R, Babu T, Bandgar TR, Bantwal G, Bhagwat NM, Chatterjee S, Jain SM, John M, Kale S, Kanungo AK, Kumar A, Kumar H, Kumar SN, Lodha S, Majumder A, Mithal A, Murthy S, Sethi BK, Shah P, Sharma SK, Sivagnanam N, Velu S, Viswanathan V, Yajnik CS, Byrne M, O'Brien T, Aimaretti G, Baroni MG, D'Amico E, Dotta F, Giordano C, Sforza A, Tonolo G, Bebakar WM, Kamaruddin NA, Hussein Z, Mumtaz M, Sothiratnam R, Gonzalez-Galvez G, Garcia Hernandez PA, Grineva E, Kalashnikova MF, Kulkova P, Krasilnikova EE, Kondrachenko S, Kunitsyna MA, Poley M, Sardinov R, Vorokhobina NV, Yurievna M, Zhdanova EA, Zhukova LA, Dalan R, Khoo EY, Sum CF, Cizova M, Martinka E, Schroner Z, Teplanova M, Tomasova L, Biermann E, Dulabh R, Khutsoane DT, Komati SM, Makan HA, Mayet L, Mitha EA, Padayachee T, Pillay S, Reddy J, Snyman HH, Siddique N, Trokis J, Romero Bobillo E, de la Cuesta C, Rivas Fernández M, Soto González A, De Teresa Parreño L, Raya PM, López de la Torre M, Merino Torres JF, Sheu WH, Sun JH, Yang CY, Deerochanawong C, Phornphutkul M, Suwanwalaikorn S, Sriwijitkamol A, Clark J, Downie P, Evans P, Furlong N, Gough S, Harper R, Harvey JN, Khan A, Leese G, McKinnon C, Narendran P, Patterson C, Raymond F, Singhal P, Smith P, Viljoen A, Willis T, Acampora M, Agaiby JM, Ahmed I, Allison JR, Altamirano D, Anderson MW, Andrawis N, Aroda VR, Ballard TV, Beavins J, Bedel GW, Bernstein R, Blaze K, Bode BW, Bononi PL, Broker RE, Buse JB, Butuk DJ, Camiscoli DJ, Canadas R, Castorino K, Cathcart H, Cha G, Chang A, Chappel CM, Cheema C, Chenore M, Cheung D, Christensen J, Chu JW, Chuck L, Cohen CD, Cohen K, Cho MH, Rivera-Colon L, Condit J, Corbett B, Pearlstein R, Cox WR, Daboul NY, Deatkine D, Dunn LJ, Ellison HS, Feldman BN, Fidelholtz J, First B, Fishman N, Fogarty CM, Fraser NJ, Gabra N, Gaona RE, Gerety G, Gilman RM, Gonte WS, Gottschlich GM, Grant DM, Hewitt M, Hollander P, House BA, Huffman D, Jain RK, Johnson G, Jones SW, Kayne DM, Kimmel MA, Klonoff D, Knight H, Koontz D, Kutner ME, Lenhard JM, Liss JL, Litchfield WR, Lubin B, Lucas KJ, Lynn L, Lyons TJ, Macadams MR, Mach MQ, Maletz L, Mariano HG, Mayeda SO, Pratley RE, Madder R, Martinez GJ, Mcgarity WC Jr, Mckenzie WC, Meisner CR, Montenegro C, Moran JE, Morawski EJ, Moretto TJ, Mudaliar SR, Murray AV, Myers L, Odugbesan AO, Olivarez E, Pangtay D, Patel MB, Patel NR, Patel R, Perdomo A, Pritchett KL, Rasmussen B, Reed JC, Reeves ML, Reichman A, Rhee C, Rice LC, Risser J, Rodbard HW, Rosen R, Rosenstock J, Ryan EH, Schreiman RC, Scott RB, Selagamsetty MR, Shaughnessy J, Silver R, Simon HJ, Snyder B, Soufer J, Stegemoller RK, Sugimoto D, Thurman J, Tolia KK, Wagner R, Wahlen J, Webster DE, Weisbrot AJ, Whittier F, Winkle PJ, Woolley JH, Yeoman G, Zemel LR, Smith BP, Philis-Tsimikas A, Weissman P, Kurland Wise J.

Author information

1
Oxford Centre for Diabetes, Endocrinology and Metabolism, and NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK. Electronic address: stephen.gough@ocdem.ox.ac.uk.
2
Atlanta Diabetes Associates, Atlanta, GA, USA.
3
Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
4
Endocrine and Metabolic Consultants, Rockville, MD, USA.
5
Coffs Harbour Diabetes Clinic, Coffs Harbour, NSW, Australia.
6
Novo Nordisk, Søborg, Denmark.
7
Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.

Abstract

BACKGROUND:

A fixed-ratio combination of the basal insulin analogue insulin degludec and the glucagon-like peptide-1 (GLP-1) analogue liraglutide has been developed as a once-daily injection for the treatment of type 2 diabetes. We aimed to compare combined insulin degludec-liraglutide (IDegLira) with its components given alone in insulin-naive patients.

METHODS:

In this phase 3, 26-week, open-label, randomised trial, adults with type 2 diabetes, HbA1c of 7-10% (inclusive), a BMI of 40 kg/m(2) or less, and treated with metformin with or without pioglitazone were randomly assigned (2:1:1) to daily injections of IDegLira, insulin degludec, or liraglutide (1·8 mg per day). IDegLira and insulin degludec were titrated to achieve a self-measured prebreakfast plasma glucose concentration of 4-5 mmol/L. The primary endpoint was change in HbA1c after 26 weeks of treatment, and the main objective was to assess the non-inferiority of IDegLira to insulin degludec (with an upper 95% CI margin of 0·3%), and the superiority of IDegLira to liraglutide (with a lower 95% CI margin of 0%). This study is registered with ClinicalTrials.gov, number NCT01336023.

FINDINGS:

1663 adults (mean age 55 years [SD 10], HbA1c 8·3% [0·9], and BMI 31·2 kg/m(2) [4·8]) were randomly assigned, 834 to IDegLira, 414 to insulin degludec, and 415 to liraglutide. After 26 weeks, mean HbA1c had decreased by 1·9% (SD 1·1) to 6·4% (1·0) with IDegLira, by 1·4% (1·0) to 6·9% (1·1) with insulin degludec, and by 1·3% (1·1) to 7·0% (1·2) with liraglutide. IDegLira was non-inferior to insulin degludec (estimated treatment difference -0·47%, 95% CI -0·58 to -0·36, p<0·0001) and superior to liraglutide (-0·64%, -0·75 to -0·53, p<0·0001). IDegLira was generally well tolerated; fewer participants in the IDegLira group than in the liraglutide group reported gastrointestinal adverse events (nausea 8·8 vs 19·7%), although the insulin degludec group had the fewest participants with gastrointestinal adverse events (nausea 3·6%). We noted no clinically relevant differences between treatments with respect to standard safety assessments, and the safety profile of IDegLira reflected those of its component parts. The number of confirmed hypoglycaemic events per patient year was 1·8 for IDegLira, 0·2 for liraglutide, and 2·6 for insulin degludec. Serious adverse events occurred in 19 (2%) of 825 patients in the IDegLira group, eight (2%) of 412 in the insulin degludec group, and 14 (3%) of 412 in the liraglutide group.

INTERPRETATION:

IDegLira combines the clinical advantages of basal insulin and GLP-1 receptor agonist treatment, resulting in improved glycaemic control compared with its components given alone.

FUNDING:

Novo Nordisk.

PMID:
25190523
DOI:
10.1016/S2213-8587(14)70174-3
[Indexed for MEDLINE]

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